Jutta Ellermann

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model.

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Functional magnetic resonance imaging of cerebellar activation during the learning of a visuomotor dissociation task

We have used functional magnetic resonance imaging (fMRI) to study the changes in cerebellar activation that occur during the acquisition of motor skill in human subjects presented with a new task. The standard paradigm consisted of a center‐out movement in which subjects used a joystick to superimposed a cursor onto viusual targets. Two variations of this paradigm were introduced: (1) a learning paradigm, where the relationship between movement of the joystick and cursor was reversed, requiring the learning of a visuomotor transformation to optimize performance and (2) a random paradigm, where the joystick/cursor relationship was changed randomly for each trial. Activation in the cerebellum was highest during the random paradigm and during the early stages of the learning paradigm. In the early stages of learning and during the random paradigm performance was poor with a decrease in the number of completed movements, and an increase in the time and length of movements. With repeated practice at the learning paradigm performance improbed and reached the same level of proficiency as in the standard task. Commensurate with the improbement in performance was a decrease in cerebellar activation, that is, activation in the cerebellum changed in a parallel, but inverse relationship with performance. Linear regression analysis demonstarated that the inverse correlation between cerebellar activation and motor performance was significant. Repeated practice at the random paradigm did not produce improvements in performance and cerebellar activity remained high. The data support the hypothesis that the cerebellum is strongly activated when motor performance is inaccurate, consistent with a role for the cerebellum in the detection of, and correction for visuomotor errors.

Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation.

&NA; Menon RS, Ogawa S, Kim S‐G, Ellermann JM, Merkle H, Tank DW, Ugurbil K. Functional brain mapping using magnetic resonance imaging: signal changes accompanying visual stimulation. Invest Radiol 1992;27:S47‐S53. Easily detectable (5%‐20%) transient increases in the intensity of water proton magnetic resonance (MR) signals in human primary visual cortex were observed during visual stimulation in gradient echo images at 4‐T field strength. The signal intensity increases were predominantly restricted to areas containing gray matter and were used to produce high‐spatial‐resolution human functional brain maps. Time dependence of the functional brain maps also was monitored during visual stimulation using images acquired every approximately 5 seconds; these images with high spatial and temporal resolution demonstrated that photic stimulation first resulted in signal increases in a large area of the visual cortex followed by a reduction in the size of the area, and that signal intensity increases in the gray matter were time dependent. Reducing the image acquisition echo times reduced the amplitude of the fractional signal change, suggesting that it is produced by a change in T2 or T2*. The amplitude, sign, and echo time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow (rCBF) with a concomitant increase in venous blood oxygenation.

Articular osteochondrosis: a comparison of naturally-occurring human and animal disease.

BACKGROUND Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. OBJECTIVE The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. STUDY DESIGN Review. METHODS The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. RESULTS A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end-stage lesion, suggesting a shared pathogenesis across species. CONCLUSION This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans.

Disc degeneration assessed by quantitative T2* (T2 Star) correlated with functional lumbar mechanics

Study Design. Experimental correlation study design to quantify features of disc health, including signal intensity and distinction between the annulus fibrosus and nucleus pulposus, with T2* magnetic resonance imaging (MRI) and correlate with the functional mechanics in corresponding motion segments. Objective. Establish the relationship between disc health assessed by quantitative T2* MRI and functional lumbar mechanics. Summary of Background Data. Degeneration leads to altered biochemistry in the disc, affecting the mechanical competence. Clinical routine MRI sequences are not adequate in detecting early changes in degeneration and fails to correlate with pain or improve patient stratification. Quantitative T2* relaxation time mapping probes biochemical features and may offer more sensitivity in assessing disc degeneration. Methods. Cadaveric lumbar spines were imaged using quantitative T2* mapping, as well as conventional T2-weighted MRI sequences. Discs were graded by the Pfirrmann scale, and features of disc health, including signal intensity (T2* intensity area) and distinction between the annulus fibrosus and nucleus pulposus (transition zone slope), were quantified by T2*. Each motion segment was subjected to pure moment bending to determine range of motion (ROM), neutral zone (NZ), and bending stiffness. Results. T2* intensity area and transition zone slope were significantly correlated with flexion ROM (P = 0.015; P = 0.002), ratio of NZ/ROM (P = 0.010; P = 0.028), and stiffness (P = 0.044; P = 0.026), as well as lateral bending NZ/ROM (P = 0.005; P = 0.010) and stiffness (P = 0.022; P = 0.029). T2* intensity area was also correlated with lateral bending ROM (P = 0.023). Pfirrmann grade was only correlated with lateral bending NZ/ROM (P = 0.001) and stiffness (P = 0.007). Conclusion. T2* mapping is a sensitive quantitative method capable of detecting changes associated with disc degeneration. Features of disc health quantified with T2* predicted altered functional mechanics of the lumbar spine better than traditional Pfirrmann grading. This new methodology and analysis technique may enhance the assessment of degeneration and enable greater patient stratification for therapeutic strategies. Level of Evidence: N/A

Multiparametric MRI assessment of human articular cartilage degeneration: Correlation with quantitative histology and mechanical properties

To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion‐prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration.

Simultaneous bilateral hip joint imaging at 7 Tesla using fast transmit B1 shimming methods and multichannel transmission – a feasibility study

The objective of this study was to demonstrate the feasibility of simultaneous bilateral hip imaging at 7 Tesla. Hip joint MRI becomes clinically critical since recent advances have made hip arthroscopy an efficacious approach to treat a variety of early hip diseases. The success of these treatments requires a reliable and accurate diagnosis of intraarticular abnormalities at an early stage. Articular cartilage assessment is especially important to guide surgical decisions but is difficult to achieve with current MR methods. Because of gains in tissue contrast and spatial resolution reported at ultra high magnetic fields, there are strong expectations that imaging the hip joint at 7 Tesla will improve diagnostic accuracy. Furthermore, there is growing evidence that the majority of these hip abnormalities occur bilaterally, emphasizing the need for bilateral imaging.

Acetabular Cartilage Assessment in Patients with Femoroacetabular Impingement by Using T2* Mapping with Arthroscopic Verification

PURPOSE To evaluate the ability of T2* mapping to help differentiate damaged from normal acetabular cartilage in patients with femoroacetabular impingement (FAI). MATERIALS AND METHODS The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The study complied with HIPAA guidelines. The authors reviewed T2* relaxation time maps of 28 hips from 26 consecutive patients (mean patient age, 28.2 years; range, 12-53 years; eight male patients (nine hips) with a mean age of 26.7 years [range, 16-53 years]; 18 female patients (19 hips) with a mean age of 28.9 years [range, 12-46 years]). Conventional diagnostic 3.0-T magnetic resonance (MR) arthrography was augmented by including a multiecho gradient-recalled echo sequence for T2* mapping. After imaging, acetabular and femoral data were separated and acetabular regions of interest were identified. Arthroscopic cartilage assessment with use of a modified Beck scale for acetabular cartilage damage was performed by an orthopedic surgeon who was blinded to the results of T2* mapping. A patient-specific acetabular projection with a T2* overlay was developed to anatomically correlate imaging data with those from surgery (the standard of reference). Results were analyzed by using receiver operating characteristic (ROC) curves. RESULTS The patient-specific acetabular projection enabled co-localization between the MR imaging and arthroscopic findings. T2* relaxation times for normal cartilage (Beck score 1, 35.3 msec ± 7.0) were significantly higher than those for cartilage with early changes (Beck score 2, 20.7 msec ± 6.0) and cartilage with more advanced degeneration (Beck scores 3-6, ≤19.8 msec ± 5.6) (P < .001). At ROC curve analysis, a T2* value of 28 msec was identified as the threshold for damaged cartilage, with a 91% true-positive and 13% false-positive rate for differentiating Beck score 1 cartilage (normal) from all other cartilages. CONCLUSION The patient-specific acetabular projection with a T2* mapping overlay enabled good anatomic localization of cartilage damage defined with a T2* threshold of 28 msec and less.

MRI rotating frame relaxation measurements for articular cartilage assessment

In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T2 and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48h in 10 bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48h. Relaxation times measured at 48h were longer than those measured at 0h in both groups. The changes in T2 and MT relaxation times after 48h were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T2 and MT. Since adiabatic T1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T1ρ methods, adiabatic T1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings.

Relaxation dispersion in MRI induced by fictitious magnetic fields

A new method entitled Relaxation Along a Fictitious Field (RAFF) was recently introduced for investigating relaxations in rotating frames of rank ≥ 2. RAFF generates a fictitious field (E) by applying frequency-swept pulses with sine and cosine amplitude and frequency modulation operating in a sub-adiabatic regime. In the present work, MRI contrast is created by varying the orientation of E, i.e. the angle ε between E and the z″ axis of the second rotating frame. When ε > 45°, the amplitude of the fictitious field E generated during RAFF is significantly larger than the RF field amplitude used for transmitting the sine/cosine pulses. Relaxation during RAFF was investigated using an invariant-trajectory approach and the Bloch-McConnell formalism. Dipole-dipole interactions between identical (like) spins and anisochronous exchange (e.g., exchange between spins with different chemical shifts) in the fast exchange regime were considered. Experimental verifications were performed in vivo in human and mouse brain. Theoretical and experimental results demonstrated that changes in ε induced a dispersion of the relaxation rate constants. The fastest relaxation was achieved at ε ≈ 56°, where the averaged contributions from transverse components during the pulse are maximal and the contribution from longitudinal components are minimal. RAFF relaxation dispersion was compared with the relaxation dispersion achieved with off-resonance spin lock T(₁ρ) experiments. As compared with the off-resonance spin lock T(₁ρ) method, a slower rotating frame relaxation rate was observed with RAFF, which under certain experimental conditions is desirable.